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PubMed2001

Transdermal delivery of nalbuphine and nalbuphine pivalate from hydrogels by passive diffusion and iontophoresis.

The objective of this study was to evaluate the in vitro transdermal permeation of nalbuphine hydrochloride (CAS 23277-43-2) (NA) and nalbuphine pivalate (NAP), a novel prodrug of NA, from different hydrogel formulations under passive diffusion as well as iontophoresis. Various concentrations of polymers, including polyvinylpyrrolidone (PVP) and hydroxypropyl cellulose (HPC) were used in the hydrogel formulations. The passive permeation rate of NA was affected by the polymer concentrations, which can be attributed to different viscosities of the hydrated formulations; whereas the passive permeation rate of NAP was not influenced by the various polymer concentrations. Iontophoresis significantly increased the permeation rates of NA and NAP from various hydrogel formulations through skin; the enhancement ratios were higher for NA in all the formulations studied. The iontophoretic permeation rates of NA were slightly decreased by the incorporation of polymers; however, the transdermal flux and membrane potential were independent of polymer concentrations for both NA and NAP, demonstrating that the polymer concentrations in the hydrogel formulations did not have significant effects on the iontophoretic permeation of NA and NAP.

Administration, Cutaneous↗
PubMed1995

Iontophoresis for modulation of cardiac drug delivery in dogs.

Cardiac arrhythmias are a frequent cause of death and morbidity. Conventional antiarrhythmia therapy involving oral or intravenous medication is often ineffective and complicated by drug-associated side effects. Previous studies from our laboratory have demonstrated the advantages of cardiac drug-polymer implants for enhanced efficacy for cardiac arrhythmia therapy compared with conventional administration. However, these studies were based on systems that deliver drugs at a fixed release rate. Modulation of the drug delivery rate has the advantage of regulating the amount of the drug delivered depending upon the disease state of the patient. We hypothesized that iontophoresis could be used to modulate cardiac drug delivery. In this study, we report our investigations of a cardiac drug implant in dogs that is capable of iontophoretic modulation of the administration of the antiarrhythmic agent sotalol. We used a heterogeneous cation-exchange membrane (HCM) as an electrically sensitive and highly efficient rate-limiting barrier on the cardiac-contacting surface of the implant. Thus, electric current is passed only through the HCM and not the myocardium. The iontophoretic cardiac implant demonstrated in vitro drug release rates that were responsive to current modulation. In vivo results in dogs have confirmed that iontophoresis resulted in regional coronary enhancement of sotalol levels with current-responsive increases in drug concentrations. We also observed acute current-dependent changes in ventricular effective refractory periods reflecting sotalol-induced refractoriness due to regional drug administration. In 30-day dog experiments, iontophoretic cardiac implants demonstrated robust sustained function and reproducible modulation of drug delivery kinetics.

Animals↗
PubMedDate not supplied

Changes in gene expression in latent HSV-1-infected rabbit trigeminal ganglia following epinephrine iontophoresis.

PURPOSE: The aim of the present study was to identify the genes that express in the nervous system when herpes simplex virus type 1 (HSV-1) reactivates from latency by using subtraction cloning following epinephrine iontophoresis. METHODS: The corneas of New Zealand White rabbits (2 to 2.5 kg) were topically inoculated with 5 x 10(5) PFU of plaque-purified HSV-1 strain McKrae. Corneal infection was monitored by slit lamp examination (SLE) on days 3-7 after infection. At 30 d post-infection, eyes were assessed for infectious virus by ocular swabs. Disappearance of virus in ocular swabs signified latency for HSV-1. Latently-infected rabbits were subjected to transcorneal iontophoresis. The messenger RNA (mRNA) was isolated from the trigeminal ganglia and used for subtraction cloning and subtraction library synthesis. RESULTS: Our results indicate 18 genes with increased expression and 6 genes with decreased levels. Northern blot analysis revealed that genes for OX-40 ligand, MHC class II HLA-DR-alpha and beta-microglobulin showed predominant increase followed by tyrosine 3'-monooxygenase, proteolipid protein, tyrosine beta, and apolipoprotein D. Genes that underwent reduced expression included cytochrome c oxidase subunit I, ATP synthase isoform, cytochrome b, ATPase 9, and at least one unidentified gene. CONCLUSIONS: Our results, particularly the increased detection of OX-40 ligand and MHC class II-alpha and beta-2 microglobulin, support the finding that lymphocytes persist in latently-infected trigeminal ganglia (TGs). These results also suggest a role of the immune system in HSV-1 recurrences. In addition, we have detected genes associated with neuronal disorders, OX-40L, proteolipid protein, and apolipoprotein D.

Animals↗
PubMed1995

Iontophoresis in the diagnosis of facial pain.

Iontophoresis is effective in anesthesia blocking for evaluating the source of pain. When extraoral anesthesia is required, the author has discovered there is less resistance from the patient if iontophoresis is offered as an alternative to needle injections in selected sites.

Anesthetics, Local↗
PubMed2004

Wavelet analysis of blood flow dynamics: effect on the individual oscillatory components of iontophoresis with pharmacologically neutral electrolytes.

Iontophoresis currents are used in the transcutaneous delivery of vasoactive substances for noninvasive assessment of skin vascular properties. The blood flow rate can be recorded by laser Doppler flowmetry (LDF), its average value and the amplitudes of its oscillatory components being used to evaluate the effect of the drugs. Because non-drug-specific, current-induced, vasodilation could confound the interpretation of the response, we have investigated the effect of currents of both polarities on the spectral components of the LDF signal in the absence of vasoactive substances. It was recorded for healthy volunteers with both high conductance (5 mol/l NaCl) and low conductance (deionized water) electrolytes. The oscillatory components were analysed by wavelet transform within 0.0095-1.6 Hz, divided into five sub-intervals. Only cathodal iontophoresis with deionized water increased the oscillatory energy and amplitude. It did so at all frequencies, but none of the sub-intervals associated with vasodilation (0.0095-0.145 Hz) was selectively affected compared to the others.

Adult↗
PubMed1985

Trans-scleral iontophoresis of gentamicin.

Bactericidal levels of gentamicin were obtained in vitreous humor by iontophoresis of antibiotic directly through the sclera. A silicone rubber tube of small diameter filled with gentamicin sulfate formed the electrode. A two milliampere current applied for three minutes to each of four perilimbal sites introduced gentamicin sufficient to maintain therapeutic levels for more than 24 hours. The proportion of drug reaching vitreous versus aqueous humor was dependent on electrode position relative to retina and pars plana. An endogenous antibacterial agent was apparently released during iontophoretic stimulation and interfered with the bacterial growth inhibition assay. Ketoconazole, a water-insoluble antifungal agent, has also been introduced successfully into vitreous humor by anodal iontophoresis after protonation in weak acid.

Animals↗
PubMed1991

Experimental transscleral iontophoresis of ciprofloxacin.

Ciprofloxacin was administered into the aqueous humor and vitreous body of the rabbit eye by transscleral iontophoresis. Positively and negatively charged forms of the drug molecule were tested. Therapeutic concentrations of ciprofloxacin were achieved in the aqueous body only when the negatively charged drug molecule was used. Ciprofloxacin did not reach the vitreous body in therapeutic concentrations in either the positively or negatively charged form, but higher concentrations were achieved when the drug was negatively charged. Peak levels were obtained in the aqueous and vitreous bodies (0.62 micrograms/ml and 0.19 micrograms/ml, respectively) one hour after transscleral iontophoresis of negatively charged ciprofloxacin at 5 mA for 15 minutes.

Animals↗
PubMed1994

The role of iontophoresis in ocular drug delivery.

Iontophoresis has been utilized in the field of ophthalmology for many years. Present application of this technique has diminished considerably and few clinicians are currently familiar with its use. This review aims to educate the reader regarding the essential features of this procedure and to discuss the past and future role of iontophoresis in ocular drug delivery.

Animals↗
PubMed1978

Antibiotic iontophoresis in the treatment of ear chondritis.

This apparently successful management of suppurative ear chondritis by employing antibiotic iontophoresis does suggest a clinical potential for the use of the procedure. The authors recommend further research to document the efficacy of this procedure as this clinical report does not involve a large sample or sufficient experimental controls, such as selection of medication, dosage values, and confirmation of tissue content of the medication. Factors favoring the trial use of antibiotic iontophoresis, particularly before the permanent disfigurement of extensive chondrectomy or amputation, are 1) reported past experimental confirmation of the effectiveness of iontherapy, 2) the expected small incidence of procedural complications, 3) the ease of application, and 4) the usual absence of discomfort.

Adult↗
PubMed2004

Assessment of endothelial function in complex regional pain syndrome type I using iontophoresis and laser Doppler imaging.

OBJECTIVES: To assess microvascular endothelial function in patients with complex regional pain syndrome type I (CRPS) compared with healthy controls, as measured by iontophoresis of vasoactive chemicals and laser Doppler imaging. METHODS: Microvascular blood flow was stimulated locally in affected and contralateral limbs of patients with CRPS (n = 17) and in control subjects (n = 16) using iontophoresis of the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (NaNP). Changes in blood flow were measured using laser Doppler imaging. Comparisons were made between right and left limbs and between patients and controls. RESULTS: No significant differences in blood flow [expressed as a median percentage increase from baseline (interquartile range)] were detected between affected and contralateral limbs in patients with CRPS for ACh [affected 237 (95-344); unaffected 251 (152-273)] or for NaNP [affected 102 (49-300); unaffected 190 (53-218)]. In addition, there were no significant differences between patients and healthy controls [controls, ACh 216 (119-316); controls, NaNP: 122 (48-249)]. CONCLUSIONS: In this pilot study, CRPS was not associated with impairment of microvascular endothelial function. This may be a true result or may reflect the diversity of the CRPS disease process.

Acetylcholine↗
PubMedDate not supplied

Reduced skin hyperemia during tap water iontophoresis after intake of acetylsalicylic acid.

Skin microcirculation and skin temperature of 10 healthy subjects (6 men and 4 women, 20-44 yr of age) without any vascular diseases were registered when a thermoindifferent tap water iontophoresis was applied. The aim of this controlled study was to evaluate the development of skin hyperemia after the intake of 500 mg of acetylsalicylic acid (ASA). The measurement was conducted by laser-Doppler flowmetry on the proximal forearm. The skin temperature was measured before and after the treatment by an infrared thermometer. In all persons there was an intense erythema on the side of the cathode and only a modest one on the side of the anode. Without ASA preliminary treatment, the cutaneous flow showed an increase of 106% at the anodal side and that of 834% at the cathodal side (P < 0.001). After ending tap water iontophoresis, the skin temperature increased more on the cathode side than on the anode side (P < 0.001). After the intake of 500 mg ASA, the increase of the flow was 78% at the anode and 88% at the cathode. The comparison of the skin microcirculation did not show any differences at the anodal side when acetylsalicylic acid was taken before, but a strong suppression of the galvanic erythema at the cathodal side was observed after the intake of ASA. There is a direct influence of acetylsalicylic acid on the induction of the neurogenic inflammation caused by a galvanic erythema. The intensity of the induced erythema correlates with the analgesic effects of constant current treatment. An attenuation of the electrotherapeutic analgesia is possible.

Adult↗
PubMed2002

Opportunities at the skin interface for continuous patient monitoring: a reverse iontophoresis model tested on lactate and glucose.

Skin has the potential to provide an important noninvasive route for diagnostic monitoring of human subjects for a wide range of applications. Dimensions of surface features in skin suggest that nanodevices and microdevices could be utilized to monitor molecules and ions extracted from the skin. Methods of enhancing extraction from the skin for diagnostics are being developed including reverse iontophoresis, electroporation and sonophoresis. A model system for the simulation of in vivo extraction of molecules and ions by reverse iontophoresis is described here that displays similar behavior to skin both in terms of molecular flux levels and electrical impedance characteristics. The device has potential for use in the development of complete reverse iontophoresis/sensor systems, allowing sensor and extraction systems to be studied and optimized before being tested in the complex in vivo environment. The system has been tested using glucose and lactate and the results are reported and discussed.

Animals↗
PubMed1999

Follow-up of clinical efficacy of iontophoresis therapy for postherpetic neuralgia (PHN).

A great variety of therapies have been attempted for PHN, including pharmacotherapy and physical therapy. However, there has been no decisive treatment, and reports of the clinical efficacy of all available therapies have been rather controversial. Almost all studies conducted so far have looked only at short-term therapeutic efficacy, and only a few investigators have conducted long-term observations or studies on long-term outcome. We followed up the clinical efficacy of iontophoresis therapy using lidocaine and methylprednisolone in 197 PHN patients. Monitoring conducted for an average of 4 years after completion of the treatment showed that pain remained unchanged or improved compared to pain observed upon completion of the treatment in 90.4% of patients. Although 42.6% of patients were still continuing some treatment, 90.9% were found to be able to take care of themselves. Findings obtained were reviewed and discussed from various viewpoints. Our findings showed that iontophoresis therapy is not only effective at the end of the treatment, but its efficacy is maintained over a long period of time, indicating that it is clinically very useful for the treatment of PHN.

Adult↗
PubMed1995

Pilocarpine iontophoresis test: an index of physiological sweat secretion?

The pilocarpine iontophoresis test (P-test) is used as a predictor of the capacity to produce sweat. Therefore, we studied the reproducibility of this test in 12 normal subjects on 10 consecutive days. Furthermore, we determined whether the P-test reflects whole-body and regional sweat secretion during exercise in the heat. Finally, we determined whether the P-test stimulates the eccrine sweat glands to maximal sweat secretion. Six growth hormone-deficient (GHD) patients who are known to have decreased sweating, and 11 healthy control subjects were studied. To induce maximal sweat secretion, the patients exercised on a bicycle ergometer at a workload corresponding to 40% of their maximal aerobic power (VO2max). The 11 healthy subjects exercised at a workload of 150 W. All subjects exercised for 60 min in ambient air at 35 degrees C, with 50% relative humidity. The P-test showed a mean day-to-day variation of 20.8% between individual subjects. There was a significant positive correlation between the P-test and regional sweat secretion (r2 = 0.74). The correlation coefficient (r2) was 0.50 for the correlation between the P-test and whole-body sweat secretion, and 0.52 for the correlation between regional sweat secretion and whole-body sweat secretion. We conclude that the pilocarpine iontophoresis test reflects heat- and exercise-induced sweating capacity. However, this test does not induce maximal sweating, and it cannot be used as a single reliable predictor of whole-body sweating, due to considerable day-to-day variation.

Adult↗
PubMed1975

Effects of CO-2 and extracellular H+ iontophoresis on single cell activity in the cat brainstem.

The activity of single cells in deep regions of the medulla oblongata was observed both during CO2 inhalation and during the extracellular iontophoresis of hydrogen ions in peripheral chemoreceptor-denervated cats. All 53 neurons that fired in synchrony with some part of the ventilatory cycle showed increased firing during CO2 inhalation; yet none responded in a graded fashion to the extracellular application of hydrogen ions. Seventy-one of the 74 nonperiodic cells studied showed no response to CO2 inhalation. Of the 3 nonperiodic cells that did respond to CO2, 2 also responded in a graded fashion to the extracellular iontophoresis of hydrogen ions. It is concluded that the cell bodies of medullary neurons with respiratory periodicity are relatively insensitive to hydrogen ions. Further the paucity of hydrogen ion-sensitive cells found in deep areas of the medulla does not support the notion that medullary hydrogen ion chemoreception is largely achieved by structures located deep in the lower brainstem.

Animals↗
PubMedDate not supplied

Ocular delivery of acetylsalicylic acid by repetitive coulomb-controlled iontophoresis.

To investigate the potential of transscleral coulomb-controlled iontophoresis (CCI) for repetitive delivery of acetylsalicylic acid (ASA) into the eye, a total of 50 rabbits was included in this study. Fourteen animals received serial CCI treatment. Fourteen animals underwent CCI with either ASA or balanced salt solution (BSS) for at least 6 days at 24- and 48-hour intervals. Eighteen animals received a single CCI application, while 18 animals were injected with 15 mg ASA/kg body weight intravenously. HPLC analysis was performed to determine the levels of salicylic acid (SA) in ocular tissues. Apart from clinical follow-up, 2 rabbits in the ASA and BSS groups were examined by electroretinography, and 2 animals were examined histologically. Though high concentrations of SA were measured, no alterations were observed clinically, histologically and electrophysiologically. Repetitive CCI demonstrated its potential as a topical drug delivery system for ASA into the eye. This transscleral delivery of ASA resulted in significant and sustained intraocular concentrations of SA without side effects. Iontophoresis may be advantageous in clinical administration maintaining therapeutic levels of ASA while avoiding adverse effects associated with the systemic administration of nonsteroidal anti-inflammatory drugs.

Animals↗
PubMed1996

Long-term outcome of iontophoresis treatment for torticollis.

In 1969, a patient with torticollis was successfully treated by a procedure called iontophoresis. Between 1958 and 1972 223 patients with torticollis were treated with this procedure. 88 of these patients (39%) were located and 56 (25% of the total, 64% of those located) returned a survey regarding their condition. 28 (13% of the total, 32% of those located, 50% of those responding) enjoyed an initial period of improvement. Of these, 16 patients (7% of the total, 18% of those located, 29% of those responding, 51% of those with initial improvement) reported sustained improvement through the time of the survey. However, 5 of these patients had additional treatment with botulinum toxin or selective denervation. We conclude that the long term effectiveness of iontophoresis treatment in the course of torticollis is minimal.

Adult↗